Hydrochloric Acid → HCID 10222020, compound

HRID 1936382Notes

Reaction equation

HRID 1936382 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:14]([CH2:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[C:15](O)=[O:16])[CH:5]=[CH:6][C:7]=1[N:8]1[C:12]([CH3:13])=[N:11][N:10]=[N:9]1.C(Cl)(=O)C(Cl)=O.[CH3:30][NH:31][C:32]([NH2:34])=[O:33].N1C=CC=CC=1.Cl>FC1C=CC=CC=1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:14]([CH2:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[C:15]([NH:34][C:32]([NH:31][CH3:30])=[O:33])=[O:16])[CH:5]=[CH:6][C:7]=1[N:8]1[C:12]([CH3:13])=[N:11][N:10]=[N:9]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 11719MethylureaHCID 65578Oxalyl chlorideHCID 11209847HCID 11209847, compound

Product 1

HCID 10222020HCID 10222020, compoundYield 31.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 10008FluorobenzeneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2-[3-chloro-4-(5-methyl-tetrazol-1-yl)-phenyl]-3-cyclopentyl-propionic acid (303 mg, 0.9 mmol) in fluorobenzene (1 mL) and NN-dimethylformamide (3 μL) at 25° C. was treated dropwise with oxalyl chloride (97 μL, 1.09 mmol) over 2-3 min. The clear solution was stirred at 25° C. for 1 h and then treated with methyl urea (201 mg, 2.72 mmol). The resulting suspension was heated at 70° C. (bath temperature) for 10 min and then treated with pyridine (146.6 μL, 1.81 mmol). The reaction mixture was then stirred at 70° C. for 20 h. The reaction mixture was then cooled to 25° C. and diluted with ethyl acetate (30 mL) and a 3N aqueous hydrochloric acid solution (30 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×20 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 1/1 hexanes/ethyl acetate) afforded 1-{2-[3-chloro-4-(5-methyl-tetrazol-1-yl)-phenyl]-3-cyclopentyl-propionyl}-3-methyl-urea (110 mg, 31%) as a white solid: mp 185-186° C. EI-HRMS m/e calcd for C18H23ClN6O2 (M+H)+ 391.1649, found 391.1659.

Workup

  1. temperatureThe resulting suspension was heated at 70° C. (bath temperature) for 10 min
  2. stirringThe reaction mixture was then stirred at 70° C. for 20 h
  3. temperatureThe reaction mixture was then cooled to 25° C.
  4. customThe two layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (1×20 mL)
  6. washThe combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL)
  7. dry with materiala saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5da1b9de857e4cfaa810ea5de46a91c9
Source dataset
uspto-grants-2002_05
Patent number
US06388088B1

Reaction notes

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